The growth of many strains of S. lactis (and L. casei) was inhibited by non-metabolizable glucose analogs including 2-deoxy-D-glucose (2DG) and 2-fluoro-2-deoxy-D-glucose. A novel futile-cycle has been discovered for 2DG-mediated inhibition of bacterial growth. In S. lactis the cycle involves three enzymatic steps: 1) accumulation of 2DG-6-phosphate via the phosphoenol-pyruvate (PEO) dependent glucose: phosphotransferase system (glucose-PTS), 2) intracellular hydrolysis of the phosphorylated derivative, and 3) efflux of free 2DG. This futile cycle promotes the dissipation of glycolytic PEP and the non-metabolizable analog functions as an uncoupler by dissociating energy generation from bacterial growth. The immunity to 2DG exhibited by some S. lactis strains is achieved by fine, and coarse regulation of the activity of the glucose-PTS. These short, and long-term responses reduce the extent of futile re-cycling and energy is conserved for growth. In separate projects it has been shown: A) that glucose-PTS defective mutants may be isolated by positive selection for resistance to 2DG, B) that separate galactose-, and lactose; PTS systems are present in L. casei and C) cells of S. lactis contain an intracellular hexose-6-phosphate phosphohydrolase and this enzyme has been purified and characterized.